Beneficial Chromosomal Integration of the Genes for CTX-M Extended-Spectrum β-Lactamase in Klebsiella pneumoniae for Stable Propagation

• Published in: mSystems Vol. 5; no. 5
• Main Authors: Yoon, Eun-Jeong, Gwon, Bareum, Liu, Changseung, Kim, Dokyun, Won, Dongju, Park, Sung Gyun, Choi, Jong Rak, Jeong, Seok Hoon
• Format: Journal Article
• Language: English
• Published: Washington American Society for Microbiology 29.09.2020
• Subjects: Addictions; Antimicrobial agents; Antimicrobial resistance; Blood; Cefotaxime; Chromosomes; Clinical Science and Epidemiology; Cloning; Drug resistance; Epidemiology; Genes; Genomes; Integration; Klebsiella pneumoniae; M gene; Plasmids; β Lactamase
• ISSN: 2379-5077; 2379-5077
• DOI: 10.1128/mSystems.00459-20

Dominant F-type plasmids harboring the gene have been pointed out to be responsible for the dissemination of the CTX-M extended-spectrum-β-lactamase (ESBL)-producing K. pneumoniae . Recently, the emergence of K. pneumoniae isolates with the bla CTX-M gene in their chromosomes has been reported occasionally worldwide. Such a chromosomal location of the resistance gene could be beneficial for stable propagation, as was the Acinetobacter baumannii ST191 harboring chromosomal bla OXA-23 that is endemic to South Korea. Through the present study, particular clones were identified as having built-in resistance genes in their chromosomes, and the chromosomal integration events were tracked by assessing their genomes. The cefotaxime-resistant K. pneumoniae clones of this study were particularized as results of the fastidiousness for plasmids to acquire the bla CTX-M gene for securing the diversity and of the chromosomal addiction of the bla CTX-M gene for ensuring propagation. ABSTRACT The acquired CTX-M-type extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales are of great concern in clinical settings because they limit therapeutic options for patients infected by the pathogens. An intriguing clonality of CTX-M ESBL-producing Klebsiella pneumoniae blood isolates was observed from a national cohort study, and comparative genomics were assessed for the 115 K. pneumoniae blood isolates carrying the bla CTX-M gene. The plasmid preference of particular clones of a sequence type (ST) was assessed by liquid mating. A quarter of the bla CTX-M gene-carrying K. pneumoniae blood isolates harbor the gene in their chromosome, and most of those with the built-in bla CTX-M gene belonged either to ST307 or ST48. Notably, all 16 K. pneumoniae ST48 isolates harbored two copies of the bla CTX-M-15 gene in the chromosome. The chromosomal integration of the bla CTX-M-15 gene was mostly derived from the IS Ecp1 -targeting 5-bp AT-rich locus in the chromosome. The IS 26 -mediated chromosomal integration occurred when the upstream IS Ecp1 from the bla CTX-M gene was truncated, targeting the anchor IS 26 copy in the chromosome. Higher transfer efficiency of the bla CTX-M-15 gene-carrying FIA:R plasmid was observed in ST17 than that of the bla CTX-M-14 gene-carrying FIB:FII plasmid. The transfer efficiency of the plasmid differed by isolate among the ST307 members. The K. pneumoniae clones ST307 and ST48 harboring the bla CTX-M-15 gene in the chromosome were able to disseminate stably in clinical settings regardless of the environmental pressure, and the current population of K. pneumoniae blood isolates was constructed. Further follow-up is needed for the epidemiology of this antimicrobial resistance. IMPORTANCE Dominant F-type plasmids harboring the gene have been pointed out to be responsible for the dissemination of the CTX-M extended-spectrum-β-lactamase (ESBL)-producing K. pneumoniae . Recently, the emergence of K. pneumoniae isolates with the bla CTX-M gene in their chromosomes has been reported occasionally worldwide. Such a chromosomal location of the resistance gene could be beneficial for stable propagation, as was the Acinetobacter baumannii ST191 harboring chromosomal bla OXA-23 that is endemic to South Korea. Through the present study, particular clones were identified as having built-in resistance genes in their chromosomes, and the chromosomal integration events were tracked by assessing their genomes. The cefotaxime-resistant K. pneumoniae clones of this study were particularized as results of the fastidiousness for plasmids to acquire the bla CTX-M gene for securing the diversity and of the chromosomal addiction of the bla CTX-M gene for ensuring propagation.